Liver fibrosis represents a continuous disease spectrum characterized by an increase in total liver collagen and other matrix proteins that disrupt the architecture of the liver and impair liver function (1, 2). The progression of fibrosis in the liver is a response to necroinflammatory changes. The overall liver fibrosis process is one of dynamic inflammation and repair and has the potential to be resolved (3). Fibrosis is seen as scar formation in the patient's liver. When the liver becomes permanently injured and scarred, the condition is called cirrhosis.
Liver fibrosis and/or cirrhosis are the major risk factors of hepatocellular carcinoma (HCC). A range of factors, such as hepatitis B virus (HBV), hepatitis C virus (HCV), hepatotoxins, metabolic disorders and alcoholism, can induce both liver fibrosis and/or cirrhosis, which share similar phenotypes (3-7), with cirrhosis being the end-stage of fibrosis. However, it is not clear what types of genes are involved or how they act when liver injury and repair occur. Moreover, the cirrhosis caused by these risk factors often progresses insidiously. Patients with end-stage liver cirrhosis can die within one year unless they accept liver transplantation, which has a 75% five-year survival rate (3).
Previous biochemical studies have reported that there are 39 well-known fibrosis or cirrhosis markers (3, 8, 9), but some markers are obtained through invasive sampling.
Studies for additional markers have proceeded based on microarray analysis of transcriptomes as well as quantitative proteomics. Microarray technologies have been widely used for comprehensive gene expression analysis. In particular, large-scale microarray analysis of gene expression enables researchers to analyze simultaneous changes in thousands of genes and identify significant patterns (10, 11). To date, the most widely used technologies in differential proteomics research were two-dimensional gel electrophoresis (2DE) and liquid chromatography-based isotope-coded affinity tagging (ICAT) technologies (12). Recently, a variation of the ICAT technology, iTRAQ (isobaric tags for relative and absolute quantitation), has been introduced. Both ICAT and iTRAQ tagging permit online identification of multiple markers and relative quantification of these proteins.